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Nutrition and Disease

Osteoclastogenesis by Bone Marrow-Derived Macrophages Is Enhanced in Obese Mice^1,2,3

⁴ Department of Biological Sciences (BK21 Program) and the Immunomodulation Research Center ⁵ Department of Food Science and Nutrition, University of Ulsan, Ulsan 680-749, Korea

Obesity induces a low-grade systemic chronic inflammatory condition for which macrophages are responsible. We hypothesized that obesity affects osteoclastogenesis by acting on bone marrow-derived macrophages (BMM). Male mice were fed a high-fat diet (45% of energy) or a standard diet (10% of energy) for 13 wk. We found that the density of the femurs of obese mice was significantly lower than that of the femurs of lean mice. Osteoclastogenesis was enhanced in the BMM from obese mice. Lower levels of interleukin (IL)-10 were generated by the BMM from obese mice than by those from lean mice upon stimulation of receptor activator of nuclear factor-B ligand. Neutralization of IL-10 in the BMM from obese mice was not as effective in increasing osteoclast (OC) formation as that in those from lean mice. Exogenous IL-10 inhibited OC formation more strongly in the BMM from obese mice than those from lean mice. The elevated level of OC formation in the BMM from obese mice may thus be due to in part to the lower level of IL-10, a negative regulator of osteoclastogenesis. Our results suggest that obesity is associated with bone loss via enhanced osteoclastogenesis due to reduced IL-10 production by the BMM from obese mice.

^* To whom correspondence should be addressed. E-mail: hschoi{at}mail.ulsan.ac.kr.

Manuscript received 25 September 2008. Initial review completed 21 October 2008. Revision accepted 23 December 2008.